Publications by authors named "Patrick Belisle"

46 Publications

Domperidone increases harmful cardiac events in Parkinson's disease: A Bayesian re-analysis of an observational study.

J Clin Epidemiol 2021 12 8;140:93-100. Epub 2021 Sep 8.

CHUM Research Center, Pavillon S, 850, St-Denis St., Montreal, Quebec, Canada; The Canadian Network for Observational Drug Effect Studies (CNODES), Jewish General Hospital, 3755 Chemin de la Côte-Sainte-Catherine H-485, Montreal, Quebec Canada; University of Montreal, 2900 Edouard Montpetit Blvd, Montreal, Quebec Canada.

Objectives: To assess the risks of ventricular tachyarrhythmia/sudden cardiac death (VT/SCD) with domperidone use in Parkinson's disease (PD).

Study Designs And Settings: Using Bayesian methods, results from an observationalstudy were combined with prior beliefs to calculate posterior probabilities of increasedrelative risk (RR)) of VT/SCD with use of domperidone compared to non-use and ofharm, defined as risk exceeding 15%. The analyses were carried with normallydistributed priors (log (RR)): uninformative (N(0,10)) or informative (N(0.53,179)),derived from a meta-analysis (OR (95%CI):1.70 (1.47-1.97)). Sensitivity analyses used:different priors' strengths, different priors, and Bayesian meta-analysis RESULTS: The uninformative prior yielded a RR: 1.23 (95% credible interval (CrI):0.94-1.62), like the published frequentist RR: 1.22 (95% CI:0.99-1.50), with 69% probabilityof harm. With an informative prior weighted at 100%, 50% and 10%, the RR were 1.63(1.41-1.88), 1.57 (1.31-1.91) and 1.39 (1.10-1.93), respectively. The correspondingprobabilities of harm were 100%, 99%, and 94%, respectively.

Conclusion: While both the frequentist and Bayesian approaches with anuninformative prior were unable to reach a definitive conclusion concerning thearrhythmic risk of domperidone in PD patients, the Bayesian analysis with informativepriors showed a high probability of increased risk that was robust to multiple priorsensitivity analyses.
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http://dx.doi.org/10.1016/j.jclinepi.2021.09.002DOI Listing
December 2021

Higher psychological distress in patients seeking care for a knee disorder is associated with diagnostic discordance between health care providers: a secondary analysis of a diagnostic concordance study.

BMC Musculoskelet Disord 2021 Jul 30;22(1):650. Epub 2021 Jul 30.

School of Rehabilitation, Faculty of Medicine, University of Montreal, Montreal, QC, Canada.

Background: Knee disorders are highly prevalent and may be a disabling condition. An accurate diagnosis is necessary to guide toward a rapid and efficient management of knee disorders. However, the ability to make a valid diagnosis is often complex for clinicians and evidence is mainly focused on clinician cognitive biases or errors produced during clinical reasoning. The aim of this secondary exploratory analysis is to identify patient-specific characteristics associated with diagnostic discordance between health care providers in making a diagnosis for a new knee disorder.

Methods: We performed a secondary analysis of a diagnostic study comparing the diagnostic ability of a physiotherapist to medical musculoskeletal specialists. Patients' socio-demographic, psychosocial and clinical characteristics were compared between the concordant and discordant diagnostic groups. Psychosocial symptoms were evaluated using the validated Kessler 6 (K6) questionnaire. We performed multivariable logistic regressions using the Bayesian Information Criterion to identify the most probable model including patients' characteristics associated with diagnostic discordance. Overall probability of identified variables to explain diagnostic discordance and associated odd ratios (OR) with 95% credibility intervals (95% CrI) were calculated.

Results: Overall, 279 participants were evaluated by a physiotherapist and medical musculoskeletal specialists. The mean age of the participants was 49.1 ± 15.8 years and 57.7% were female. The most common disorder was osteoarthritis (n = 117, 18.8% of cases were discordant). The most probable model explaining diagnostic discordance (11.13%) included having depressive symptoms, which was associated with an increased probability of diagnostic discordance (OR: 3.9; 95% CrI: 1.9 - 8.0) and having a higher number of comorbidities, which was associated with a decreased probability of diagnostic discordance (OR: 0.6; 95% CrI: 0.5 - 0.9). The depression item of the K6 questionnaire had a 99.4% chance to be included in a model explaining diagnostic discordance. Other variables taken separately had less than 50% chance to be included in a model explaining diagnostic discordance and cannot be considered significant.

Conclusion: Our results suggest that depressive symptoms may increase the risk of knee diagnostic discordance. Clinicians may be more likely to make diagnostic errors and should be more cautious when evaluating patients with knee disorders suffering from psychological distress.
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http://dx.doi.org/10.1186/s12891-021-04534-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8325325PMC
July 2021

Immediate vs Delayed Stenting in ST-Elevation Myocardial Infarction: Rationale and Design of the International PRIMACY Bayesian Randomized Controlled Trial.

Can J Cardiol 2020 11 25;36(11):1805-1814. Epub 2020 Jan 25.

Hospital of Annecy, Centre Hospitalier Annecy Genevois, Annecy, France.

Background: Primary percutaneous coronary intervention is used to restore blood flow in the infarct-related coronary artery, followed by immediate stenting to prevent reocclusion. Stents implanted in thrombus-laden arteries cause distal embolization, which paradoxically impairs myocardial reperfusion and ventricular function. Whether a strategy of delayed stenting improves outcomes in patients with acute ST-elevation myocardial infarction (STEMI) is uncertain.

Methods: The Primary Reperfusion Secondary Stenting (PRIMACY) is a Bayesian prospective, randomized, open-label, blinded end point trial in which delayed vs immediate stenting in patients with STEMI were compared for prevention of cardiovascular death, nonfatal myocardial infarction, heart failure, or unplanned target vessel revascularization at 9 months. All participants were immediately reperfused, but those assigned to the delayed arm underwent stenting after an interval of 24 to 48 hours. This interval was bridged with antithrombin therapy to reduce thrombus burden. In the principal Bayesian hierarchical random effects analysis, data from exchangeable trials will be combined into a study prior and updated with PRIMACY into a posterior probability of efficacy.

Results: A total of 305 participants were randomized across 15 centres in France and Canada between April 2014 and September 2017. At baseline, the median age of participants was 59 years, 81% were male, and 3% had a history of percutaneous coronary intervention. Results from PRIMACY will be updated from the patient-level data of 1568 participants enrolled in the Deferred Stent Trial in STEMI (DEFER; United Kingdom), Minimalist Immediate Mechanical Intervention (MIMI; France), Danish Trial in Acute Myocardial Infarction-3 (DANAMI-3; Denmark), and Impact of Immediate Stent Implantation Versus Deferred Stent Implantation on Infarct Size and Microvascular Perfusion in Patients With ST Segment-Elevation Myocardial Infarction (INNOVATION, South Korea) trials.

Conclusions: We expect to clarify whether delayed stenting can safely reduce the occurrence of adverse cardiovascular end points compared with immediate stenting in patients with STEMI.
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http://dx.doi.org/10.1016/j.cjca.2020.01.019DOI Listing
November 2020

Bayesian consensus-based sample size criteria for binomial proportions.

Stat Med 2019 10 11;38(23):4566-4573. Epub 2019 Jul 11.

Division of Clinical Epidemiology, McGill University Health Centre, Montreal, QC, Canada.

Many sample size criteria exist. These include power calculations and methods based on confidence interval widths from a frequentist viewpoint, and Bayesian methods based on credible interval widths or decision theory. Bayesian methods account for the inherent uncertainty of inputs to sample size calculations through the use of prior information rather than the point estimates typically used by frequentist methods. However, the choice of prior density can be problematic because there will almost always be different appreciations of the past evidence. Such differences can be accommodated a priori by robust methods for Bayesian design, for example, using mixtures or ϵ-contaminated priors. This would then ensure that the prior class includes divergent opinions. However, one may prefer to report several posterior densities arising from a "community of priors," which cover the range of plausible prior densities, rather than forming a single class of priors. To date, however, there are no corresponding sample size methods that specifically account for a community of prior densities in the sense of ensuring a large-enough sample size for the data to sufficiently overwhelm the priors to ensure consensus across widely divergent prior views. In this paper, we develop methods that account for the variability in prior opinions by providing the sample size required to induce posterior agreement to a prespecified degree. Prototypic examples to one- and two-sample binomial outcomes are included. We compare sample sizes from criteria that consider a family of priors to those that would result from previous interval-based Bayesian criteria.
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http://dx.doi.org/10.1002/sim.8316DOI Listing
October 2019

Pneumococcal pneumonia prevalence among adults with severe acute respiratory illness in Thailand - comparison of Bayesian latent class modeling and conventional analysis.

BMC Infect Dis 2019 May 15;19(1):423. Epub 2019 May 15.

Division of Global Health Protection, Thailand Ministry of Public Health-US Centers for Disease Control and Prevention Collaboration, Nonthaburi, Thailand.

Background: Determining the etiology of pneumonia is essential to guide public health interventions. Diagnostic test results, including from polymerase chain reaction (PCR) assays of upper respiratory tract specimens, have been used to estimate prevalence of pneumococcal pneumonia. However limitations in test sensitivity and specificity and the specimen types available make establishing a definitive diagnosis challenging. Prevalence estimates for pneumococcal pneumonia could be biased in the absence of a true gold standard reference test for detecting Streptococcus pneumoniae.

Methods: We conducted a case control study to identify etiologies of community acquired pneumonia (CAP) from April 2014 through August 2015 in Thailand. We estimated the prevalence of pneumococcal pneumonia among adults hospitalized for CAP using Bayesian latent class models (BLCMs) incorporating results of real-time polymerase chain reaction (qPCR) testing of upper respiratory tract specimens and a urine antigen test (UAT) from cases and controls. We compared the prevalence estimate to conventional analyses using only UAT as a reference test.

Results: The estimated prevalence of pneumococcal pneumonia was 8% (95% CI: 5-11%) by conventional analyses. By BLCM, we estimated the prevalence to be 10% (95% CrI: 7-16%) using binary qPCR and UAT results, and 11% (95% CrI: 7-17%) using binary UAT results and qPCR cycle threshold (Ct) values.

Conclusions: BLCM suggests a > 25% higher prevalence of pneumococcal pneumonia than estimated by a conventional approach assuming UAT as a gold standard reference test. Higher quantities of pneumococcal DNA in the upper respiratory tract were associated with pneumococcal pneumonia in adults but the addition of a second specific pneumococcal test was required to accurately estimate disease status and prevalence. By incorporating the inherent uncertainty of diagnostic tests, BLCM can obtain more reliable estimates of disease status and improve understanding of underlying etiology.
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http://dx.doi.org/10.1186/s12879-019-4067-3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6521483PMC
May 2019

The Measurable Benefits of a Workplace Wellness Program in Canada: Results After One Year.

J Occup Environ Med 2018 03;60(3):211-216

McGill Comprehensive Health Improvement Program, Montreal, Quebec, Canada (Drs Lowensteyn, DaCosta, Grover); Division of Clinical Epidemiology, Department of Medicine, McGill University, Montreal, Quebec, Canada (Dr Lowensteyn, Mr Belisle, Drs DaCosta, Joseph, Grover); Merck Canada Inc., Kirkland, Quebec, Canada (Ms Berberian); and Department of Epidemiology, Biostatistics and Occupational Health, McGill University, Montreal, Quebec, Canada (Dr Joseph).

Objective: The aim of this study was to evaluate the impact of an employee wellness program in Canada.

Methods: A comprehensive program including web-based lifestyle challenges was evaluated with annual health screenings.

Results: Among 730 eligible employees, 688 (94%) registered for the program, 571 (78%) completed a health screening at baseline, and 314 (43%) at 1 year. Most (66%) employees tracked their activity for more than 6 weeks. At 1-year follow-up, there were significant clinical improvements in systolic blood pressure -3.4 mm Hg, and reductions in poor sleep quality (33% to 28%), high emotional stress (21% to 15%), and fatigue (11% to 6%). A positive dose-response was noted where the greatest improvements were observed among those who participated the most.

Conclusion: The program had high employee engagement. After 1 year, the benefits included clinically important improvements in physical and mental health.
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http://dx.doi.org/10.1097/JOM.0000000000001240DOI Listing
March 2018

Clinically Apparent Arterial Thrombosis in Persons with Systemic Vasculitis.

Int J Rheumatol 2017 21;2017:3572768. Epub 2017 Jun 21.

Division of Rheumatology, Department of Medicine, McGill University Health Centre, Montreal, QC, Canada.

Objective: To estimate the incidence rate of clinically apparent arterial thrombotic events and associated comorbidities in patients with primary systemic vasculitis.

Methods: Using large cohort administrative data from Quebec, Canada, we identified patients with vasculitis, including polyarteritis nodosa (PAN) and granulomatosis with polyangiitis (GPA). Incident acute myocardial infarctions (AMIs) and cerebrovascular accidents (CVAs) after the diagnosis of vasculitis were ascertained in the PAN and GPA group via billing and hospitalization data. These were compared to rates of a general population comparator group. The incidences of comorbidities (type 2 diabetes mellitus, dyslipidemia, and hypertension) were also collected.

Results: Among the 626 patients identified with vasculitis, 19.7% had PAN, 2.9% had Kawasaki disease, 23.8% had GPA, 52.4% had GCA, and 1.3% had Takayasu arteritis. The AMI rate was substantially higher in males aged 18-44 with PAN, with rates up to 268.1 events per 10,000 patient years [95% CI 67.1-1070.2], approximately 30 times that in the age- and sex-matched control group. The CVA rate was also substantially higher, particularly in adults aged 45-65. Patients with vasculitis had elevated incidences of diabetes, dyslipidemia, and hypertension versus the general population.

Conclusion: Atherothrombotic rates were elevated in patients identified as having primary systemic vasculitis. While incident rates of cardiovascular comorbidities were also increased, the substantial elevation in AMIs seen in young adults suggests a disease-specific component which requires further investigation.
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http://dx.doi.org/10.1155/2017/3572768DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5497634PMC
June 2017

Fine particulate air pollution and systemic autoimmune rheumatic disease in two Canadian provinces.

Environ Res 2016 Apr 24;146:85-91. Epub 2015 Dec 24.

Department of Epidemiology, Biostatistics and Occupational Health, McGill University, Purvis Hall 1020 Pine Avenue West, Montreal, QC, Canada H3A 1A2; Division of Clinical Epidemiology, McGill University Health Centre, Royal Victoria Hospital, V Pavilion 687, Pine Avenue West, Montreal, QC, Canada H3A 1A1.

Objective: To estimate the degree to which fine particulate (PM2.5) air pollution is associated with systemic autoimmune rheumatic diseases (SARDs).

Methods: We used population-based administrative data from Alberta (1993-2007) and Quebec (1989-2011). SARD algorithms included ≥2 physician billing codes, or ≥1 rheumatology billing code, or ≥1 hospitalization diagnostic code (for systemic lupus, Sjogren's Syndrome, scleroderma, polymyositis, dermatomyositis, or undifferentiated connective tissue disease). Bayesian hierarchical latent class regression models estimated the probability that any given resident was a SARD case, based on the algorithms. Mean 2001-2006 residential ambient PM2.5 levels were assigned using satellite-derived data for dissemination area regions in Alberta and CLSC regions in Quebec. The sum of individual level probabilities provided the estimated total cases per region in each province, according to age, sex, urban-versus-rural residence, income, and PM2.5 levels. In Alberta, we ran separate models for First-Nations (FN) and non-First Nations subgroups. Bayesian logistic regression modeling generated odds ratio (OR) estimates for being a SARD case, accounting concurrently for demographics, as well as an interaction term between age and sex.

Results: Our data suggested that the probability of being a SARD case was higher among females versus males and for residents aged >45 versus younger, with the highest ORs for older females. Independently, the odds of being a SARDs case increased with PM2.5 levels in both provinces.

Conclusion: Our data suggest that PM2.5 exposure may be associated with an increased risk of SARDs.
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http://dx.doi.org/10.1016/j.envres.2015.12.021DOI Listing
April 2016

Associations between neighbourhood walkability and daily steps in adults: a systematic review and meta-analysis.

BMC Public Health 2015 Aug 11;15:768. Epub 2015 Aug 11.

Department of Epidemiology, Biostatistics and Occupational Health, McGill University, 1020 Pine Avenue West, Montréal, QC, Canada.

Background: Higher street connectivity, land use mix and residential density (collectively referred to as neighbourhood walkability) have been linked to higher levels of walking. The objective of our study was to summarize the current body of knowledge on the association between neighbourhood walkability and biosensor-assessed daily steps in adults.

Methods: We conducted a systematic search of PubMed, SCOPUS, and Embase (Ovid) for articles published prior to May 2014 on the association between walkability (based on Geographic Information Systems-derived street connectivity, land use mix, and/or residential density) and daily steps (pedometer or accelerometer-assessed) in adults. The mean differences in daily steps between adults living in high versus low walkable neighbourhoods were pooled across studies using a Bayesian hierarchical model.

Results: The search strategy yielded 8,744 unique abstracts. Thirty of these underwent full article review of which six met the inclusion criteria. Four of these studies were conducted in Europe and two were conducted in Asia. A meta-analysis of four of these six studies indicates that participants living in high compared to low walkable neighbourhoods accumulate 766 more steps per day (95 % credible interval 250, 1271). This accounts for approximately 8 % of recommended daily steps.

Conclusions: The results of European and Asian studies support the hypothesis that higher neighbourhood walkability is associated with higher levels of biosensor-assessed walking in adults. More studies on this association are needed in North America.
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http://dx.doi.org/10.1186/s12889-015-2082-xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4532296PMC
August 2015

Fine particulate air pollution, nitrogen dioxide, and systemic autoimmune rheumatic disease in Calgary, Alberta.

Environ Res 2015 Jul 16;140:474-8. Epub 2015 May 16.

Department of Medicine, McGill University, Montreal, Quebec, Canada; Division of Clinical Epidemiology, McGill University Health Centre, Montreal, Quebec, Canada.

Objective: To estimate the association between fine particulate (PM2.5) and nitrogen dioxide (NO2) pollution and systemic autoimmune rheumatic diseases (SARDs).

Methods: Associations between ambient air pollution (PM2.5 and NO2) and SARDs were assessed using land-use regression models for Calgary, Alberta and administrative health data (1993-2007). SARD case definitions were based on ≥2 physician claims, or ≥1 rheumatology billing code; or ≥1 hospitalization code (for systemic lupus, Sjogren's Syndrome, scleroderma, polymyositis, dermatomyositis, or undifferentiated connective tissue disease). Bayesian hierarchical latent class regression models estimated the probability that each resident was a SARD case, based on these case definitions. The sum of individual level probabilities provided the estimated number of cases in each area. The latent class model included terms for age, sex, and an interaction term between age and sex. Bayesian logistic regression models were used to generate adjusted odds ratios (OR) for NO2 and PM2.5. pollutant models, adjusting for neighbourhood income, age, sex, and an interaction between age and sex. We also examined models stratified for First-Nations (FN) and non-FN subgroups.

Results: Residents that were female and/or aged >45 had a greater probability of being a SARD case, with the highest OR estimates for older females. Independently, the odds of being a SARDs case increased with PM2.5 levels, but the results were inconclusive for NO2. The results stratified by FN and non-FN groups were not distinctly different.

Conclusion: In this urban Canadian sample, adjusting for demographics, exposure to PM2.5 was associated with an increased risk of SARDs. The results for NO2 were inconclusive.
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http://dx.doi.org/10.1016/j.envres.2015.05.007DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4492844PMC
July 2015

Estimating risk of emergency room visits for asthma from personal versus fixed site measurements of NO2.

Environ Res 2015 Feb 17;137:323-8. Epub 2015 Jan 17.

McGill University Health Center, Division of Clinical Epidemiology, Montreal, Canada; McGill University, Department of Epidemiology, Biostatistics and Occupational Health, Montreal, Canada.

Background: We examined the impact of data source and exposure measurement error for ambient NO2 on risk estimates derived from a case-crossover study of emergency room visits for asthma in Windsor, Canada between 2002 and 2009.

Methods: Paired personal and fixed-site NO2 data were available from an independent population (47 children and 48 adults) in Windsor between 2005 and 2006. We used linear regression to estimate the relationship and measurement error variance induced between fixed site and personal measurements of NO2, and through a series of simulations, evaluated the potential for a Bayesian model to adjust for this change in scale and measurement error. Finally, we re-analyzed data from the previous case-crossover study adjusting for the estimated change in slope and measurement error.

Results: Correlations between paired NO2 measurements were weak (R(2)≤0.08) and slopes were far from unity (0.0029≤β≤0.30). Adjusting the previous case-crossover analysis suggested a much stronger association between personal NO2 (per 1ppb) (Odds Ratio (OR)=1.276, 95% Credible Interval (CrI): 1.034, 1.569) and emergency room visits for asthma among children relative to the fixed-site estimate (OR=1.024, 95% CrI 1.004-1.045).

Conclusions: Our findings suggest that risk estimates based on fixed-site NO2 concentrations may differ substantially from estimates based on personal exposures if the change in scale and/or measurement error is large. In practice, one must always keep the scale being used in mind when interpreting risk estimates and not assume that coefficients for ambient concentrations reflect risks at the personal level.
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http://dx.doi.org/10.1016/j.envres.2015.01.006DOI Listing
February 2015

Rheumatoid arthritis prevalence in Quebec.

BMC Res Notes 2014 Dec 19;7:937. Epub 2014 Dec 19.

Division of Clinical Epidemiology, McGill University Health Centre, 687 Pine Avenue West, V-Building, V2.09, Montreal, QC, H3A 1A1, Canada.

Background: To estimate rheumatoid arthritis (RA) prevalence in Quebec using administrative health data, comparing across regions.

Methods: Cases of RA were ascertained from physician billing and hospitalization data, 1992-2008. We used three case definitions: 1) ≥ 2 billing diagnoses, submitted by any physician, ≥ 2 months apart, but within 2 years; 2) ≥ 1 diagnosis, by a rheumatologist; 3) ≥1 hospitalization diagnosis (all based on ICD-9 code 714, and ICD-10 code M05). We combined data across these three case definitions, using Bayesian hierarchical latent class models to estimate RA prevalence, adjusting for the imperfect sensitivity and specificity of the data. We compared urban versus rural regions.

Results: Using our case definitions and no adjustment for error, we defined 75,760 cases for an over-all RA prevalence of 9.9 per thousand residents. After adjusting for the imperfect sensitivity and specificity of our case definition algorithms, we estimated Quebec RA prevalence at 5.6 per 1000 females and 4.1 per 1000 males. The adjusted RA prevalence estimates for older females were the highest for any demographic group (9.9 cases per 1,000), and were similar in rural and urban regions. In younger males and females, and in older males, RA prevalence estimates were lower in rural versus urban areas.

Conclusions: Without adjustment for error inherent in administrative databases, RA prevalence in Quebec was approximately 1%, while adjusted estimates are approximately half that. The lower prevalence in rural areas, seen for most demographic groups, may suggest either true regional variations in RA risk, or under-ascertainment of cases in rural Quebec.
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http://dx.doi.org/10.1186/1756-0500-7-937DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4417509PMC
December 2014

The prevalence of systemic autoimmune rheumatic diseases in Canadian pediatric populations: administrative database estimates.

Rheumatol Int 2015 Mar 26;35(3):569-73. Epub 2014 Sep 26.

Department of Paediatrics, Royal University Hospital, University of Saskatchewan, 103 Hospital Drive, Saskatoon, SK, S7N 0W8, Canada,

To estimate systemic autoimmune rheumatic disease (SARD) prevalence using administrative data for pediatric populations in four Canadian provinces. Physician billing claims and inpatient hospitalizations from Alberta, Manitoba, Quebec, and Saskatchewan were used to define cases aged ≤18 years with a SARD diagnosis code in: one or more hospitalization, two or more physician visits within 2 years and at least 2 months apart, or one or more physician visit to a rheumatologist. Estimates ranged from 15.9/100,000 in Quebec [95% confidence interval (95% CI) 14.1, 18.0] to 23.0/100,000 in Manitoba (95% CI 17.9, 29.2). SARDs were more common in females than in males across all provinces. There was a slightly higher prevalence among those living in urban compared to rural areas of Alberta (rate difference 14.4, 95% CI 8.6, 20.1) and Saskatchewan (rate difference 13.8, 95% CI 1.0, 26.6). Our results provide population-based prevalence estimates of pediatric SARDs in four Canadian provinces.
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http://dx.doi.org/10.1007/s00296-014-3136-6DOI Listing
March 2015

Chronic inflammatory arthritis prevalence estimates for children and adolescents in three Canadian provinces.

Rheumatol Int 2015 Feb 15;35(2):345-50. Epub 2014 Jul 15.

Department of Paediatrics, Royal University Hospital, University of Saskatchewan, 103 Hospital Drive, Saskatoon, SK, S7N 0C8, Canada,

There is a paucity of published population-based estimates of the prevalence of chronic inflammatory arthritis in the pediatric population. We used administrative health data to estimate the prevalence of chronic inflammatory arthritis in individuals ≤18 years in three Canadian provinces: Quebec, Manitoba, and Saskatchewan. Cases aged ≤18 years were identified by meeting any one of the following criteria: (a) ≥1 hospital discharge abstract with an ICD-9 code of 714 or ICD-10-CA codes of M05, M06 or M08, or (b) ≥2 ICD-9 714 billing codes ≥8 weeks apart, but within 2 years, or (c) ≥1 ICD-9 714 billing code by a rheumatologist. Crude prevalence estimates per 10,000 population were estimated with 95 % confidence intervals (CIs). Prevalence estimates were 11.7 per 10,000 individuals ≤18 years of age in Manitoba, 9.8 per 10,000 in Saskatchewan, and 8.0 per 10,000 in Quebec. In pairwise comparisons of rate differences, Manitoba and Saskatchewan had higher estimates than Quebec. Prevalence estimates were higher for females than males, with a difference of 5.9 cases per 10,000 residents (95 % CI 5.1, 6.7). Saskatchewan was the only province with a higher estimate in urban compared to rural residents (5.2, 95 % CI 2.5, 8.0). Variations in provincial estimates may be due to differences in underlying population characteristics. Although these estimates have face validity and are in keeping with the range of previously published pediatric prevalence estimates, studies to establish the empiric validity of case-finding algorithms are needed to advance research in pediatric chronic disease epidemiology.
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http://dx.doi.org/10.1007/s00296-014-3085-0DOI Listing
February 2015

Electrocardiographic findings in systemic lupus erythematosus: data from an international inception cohort.

Arthritis Care Res (Hoboken) 2015 Jan;67(1):128-35

University of Montreal Health Center, Montreal, Quebec, Canada.

Objective: To estimate the early prevalence of various electrocardiographic (EKG) abnormalities in patients with systemic lupus erythematosus (SLE) and to evaluate possible associations between repolarization changes (increased corrected QT [QTc] and QT dispersion [QTd]) and clinical and laboratory variables, including the anti-Ro/SSA level and specificity (52 or 60 kd).

Methods: We studied adult SLE patients from 19 centers participating in the Systemic Lupus International Collaborating Clinics (SLICC) Inception Registry. Demographics, disease activity (Systemic Lupus Erythematosus Disease Activity Index 2000 [SLEDAI-2K]), disease damage (SLICC/American College of Rheumatology Damage Index [SDI]), and laboratory data from the baseline or first followup visit were assessed. Multivariate logistic and linear regression models were used to asses for any cross-sectional associations between anti-Ro/SSA and EKG repolarization abnormalities.

Results: For the 779 patients included, mean ± SD age was 35.2 ± 13.8 years, 88.4% were women, and mean ± SD disease duration was 10.5 ± 14.5 months. Mean ± SD SLEDAI-2K score was 5.4 ± 5.6 and mean ± SD SDI score was 0.5 ± 1.0. EKG abnormalities were frequent and included nonspecific ST-T changes (30.9%), possible left ventricular hypertrophy (5.4%), and supraventricular arrhythmias (1.3%). A QTc ≥440 msec was found in 15.3%, while a QTc ≥460 msec was found in 5.3%. Mean ± SD QTd was 34.2 ± 14.7 msec and QTd ≥40 msec was frequent (38.1%). Neither the specificity nor the level of anti-Ro/SSA was associated with QTc duration or QTd, although confidence intervals were wide. Total SDI was significantly associated with a QTc interval exceeding 440 msec (odds ratio 1.38 [95% confidence interval 1.06, 1.79]).

Conclusion: A substantial proportion of patients with recent-onset SLE exhibited repolarization abnormalities, although severe abnormalities were rare.
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http://dx.doi.org/10.1002/acr.22370DOI Listing
January 2015

Systemic autoimmune rheumatic disease prevalence in Canada: updated analyses across 7 provinces.

J Rheumatol 2014 Apr 1;41(4):673-9. Epub 2014 Mar 1.

From the Division of Clinical Epidemiology, and Divisions of Rheumatology, and Clinical Immunology/Allergy, Research Institute of the McGill University Health Centre (MUHC), Montreal, Quebec; Division of Rheumatology, University of British Columbia, Vancouver, British Columbia; Department of Epidemiology and Biostatistics, and Division of Rheumatology, McGill University; Dalhousie University and Queen Elizabeth II Health Sciences Center, Halifax, Nova Scotia; Departments of Medicine and Community Health Sciences, University of Manitoba, and Repository, Manitoba Centre for Health Policy, Winnipeg, Manitoba; Centre for Chronic Disease Prevention, Public Health Agency of Canada, Ottawa, Ontario; Division of Rheumatology, University of Calgary, Calgary, Alberta; Centre de recherche du CHU de Québec, Faculté de médecine, Université Laval, Quebec City, Quebec; Chronic Disease Surveillance Division, National Institute of Public Health of Québec; Health Surveillance Branch, Public Health Division, Alberta Health and Wellness, Edmonton, Alberta; Divisions of Rheumatology, and Clinical Immunology/Allergy, Research Institute of the MUHC; Canadian Arthritis Patient Alliance; Toronto Western Research Institute, University Health Network, Toronto, Ontario, Canada.

Objective: To estimate systemic autoimmune rheumatic disease (SARD) prevalence across 7 Canadian provinces using population-based administrative data evaluating both regional variations and the effects of age and sex.

Methods: Using provincial physician billing and hospitalization data, cases of SARD (systemic lupus erythematosus, scleroderma, primary Sjögren syndrome, polymyositis/dermatomyositis) were ascertained. Three case definitions (rheumatology billing, 2-code physician billing, and hospital diagnosis) were combined to derive a SARD prevalence estimate for each province, categorized by age, sex, and rural/urban status. A hierarchical Bayesian latent class regression model was fit to account for the imperfect sensitivity and specificity of each case definition. The model also provided sensitivity estimates of different case definition approaches.

Results: Prevalence estimates for overall SARD ranged between 2 and 5 cases per 1000 residents across provinces. Similar demographic trends were evident across provinces, with greater prevalence in women and in persons over 45 years old. SARD prevalence in women over 45 was close to 1%. Overall sensitivity was poor, but estimates for each of the 3 case definitions improved within older populations and were slightly higher for men compared to women.

Conclusion: Our results are consistent with previous estimates and other North American findings, and provide results from coast to coast, as well as useful information about the degree of regional and demographic variations that can be seen within a single country. Our work demonstrates the usefulness of using multiple data sources, adjusting for the error in each, and providing estimates of the sensitivity of different case definition approaches.
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http://dx.doi.org/10.3899/jrheum.130667DOI Listing
April 2014

Bayesian sample size determination for case-control studies when exposure may be misclassified.

Am J Epidemiol 2013 Dec 12;178(11):1673-9. Epub 2013 Sep 12.

Odds ratios are frequently used for estimating the effect of an exposure on the probability of disease in case-control studies. In planning such studies, methods for sample size determination are required to ensure sufficient accuracy in estimating odds ratios once the data are collected. Often, the exposure used in epidemiologic studies is not perfectly ascertained. This can arise from recall bias, the use of a proxy exposure measurement, uncertain work exposure history, and laboratory or other errors. The resulting misclassification can have large impacts on the accuracy and precision of estimators, and specialized estimation techniques have been developed to adjust for these biases. However, much less work has been done to account for the anticipated decrease in the precision of estimators at the design stage. Here, we develop methods for sample size determination for odds ratios in the presence of exposure misclassification by using several interval-based Bayesian criteria. By using a series of prototypical examples, we compare sample size requirements after adjustment for misclassification with those required when this problem is ignored. We illustrate the methods by planning a case-control study of the effect of late introduction of peanut to the diet of children to the subsequent development of peanut allergy.
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http://dx.doi.org/10.1093/aje/kwt181DOI Listing
December 2013

Time variability of C-reactive protein: implications for clinical risk stratification.

PLoS One 2013 8;8(4):e60759. Epub 2013 Apr 8.

Quebec Heart and Lung Institute, Laval University, Quebec City, Quebec, Canada.

Background: C-reactive protein (CRP) is proposed as a screening test for predicting risk and guiding preventive approaches in coronary artery disease (CAD). However, the stability of repeated CRP measurements over time in subjects with and without CAD is not well defined. We sought to determine the stability of serial CRP measurements in stable subjects with distinct CAD manifestations and a group without CAD while carefully controlling for known confounders.

Methods: We prospectively studied 4 groups of 25 stable subjects each 1) a history of recurrent acute coronary events; 2) a single myocardial infarction ≥7 years ago; 3) longstanding CAD (≥7 years) that had never been unstable; 4) no CAD. Fifteen measurements of CRP were obtained to cover 21 time-points: 3 times during one day; 5 consecutive days; 4 consecutive weeks; 4 consecutive months; and every 3 months over the year. CRP risk threshold was set at 2.0 mg/L. We estimated variance across time-points using standard descriptive statistics and Bayesian hierarchical models.

Results: Median CRP values of the 4 groups and their pattern of variability did not differ substantially so all subjects were analyzed together. The median individual standard deviation (SD) CRP values within-day, within-week, between-weeks and between-months were 0.07, 0.19, 0.36 and 0.63 mg/L, respectively. Forty-six percent of subjects changed CRP risk category at least once and 21% had ≥4 weekly and monthly CRP values in both low and high-risk categories.

Conclusions: Considering its large intra-individual variability, it may be problematic to rely on CRP values for CAD risk prediction and therapeutic decision-making in individual subjects.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0060759PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3620269PMC
October 2013

Association of smoking with cutaneous manifestations in systemic lupus erythematosus.

Arthritis Care Res (Hoboken) 2013 Aug;65(8):1275-80

McGill University, Montreal, Quebec, Canada.

Objective: To examine the association between smoking and cutaneous involvement in systemic lupus erythematosus (SLE).

Methods: We analyzed data from a multicenter Canadian SLE cohort. Mucocutaneous involvement was recorded at the most recent visit using the Systemic Lupus Erythematosus Disease Activity Index 2000 Update (rash, alopecia, and oral ulcers), Systemic Lupus International Collaborating Clinics/American College of Rheumatology (ACR) Damage Index (alopecia, extensive scarring, and skin ulceration), and the ACR revised criteria for SLE (malar rash, discoid rash, photosensitivity, and mucosal involvement). Multivariate logistic regression models were used to estimate the independent association between mucocutaneous involvement and cigarette smoking, age, sex, ethnicity, lupus duration, medications, and laboratory data.

Results: In our cohort of 1,346 patients (91.0% women), the mean ± SD age was 47.1 ± 14.3 years and the mean ± SD disease duration was 13.2 ± 10.0 years. In total, 41.2% of patients were ever smokers, 14.0% current smokers, and 27.1% past smokers. Active mucocutaneous manifestations occurred in 28.4% of patients; cutaneous damage occurred in 15.4%. Regarding the ACR criteria, malar rash was noted in 59.5%, discoid rash in 16.9%, and photosensitivity in 55.7% of patients. In the multivariate analysis, current smoking was associated with active SLE rash (odds ratio [OR] 1.63 [95% confidence interval (95% CI) 1.07, 2.48]). Having ever smoked was associated with ACR discoid rash (OR 2.36 [95% CI 1.69, 3.29]) and photosensitivity (OR 1.47 [95% CI 1.11, 1.95]), and with the ACR total cutaneous score (OR 1.50 [95% CI 1.22, 1.85]). We did not detect any associations between previous smoking and active cutaneous manifestations. No association was found between smoking and cutaneous damage or mucosal ulcers. No interaction was seen between smoking and antimalarials.

Conclusion: Current smoking is associated with active SLE rash, and ever smoking with the ACR total cutaneous score. This provides additional motivation for smoking cessation in SLE.
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http://dx.doi.org/10.1002/acr.21966DOI Listing
August 2013

Personal exposure to specific volatile organic compounds and acute changes in lung function and heart rate variability among urban cyclists.

Environ Res 2012 Oct 8;118:118-23. Epub 2012 Jul 8.

Health Canada, Air Health Sciences Division, Ottawa, ON, Canada.

Background: Few studies have examined the acute cardiorespiratory effects of specific volatile organic compound (VOC) exposures from traffic pollution.

Methods: A cross-over study was conducted among 42 healthy adults during summer 2010 in Ottawa, Canada. Participants cycled for 1-h along high and low-traffic routes and VOC exposures were determined along each route. Lung function, exhaled nitric oxide, and heart rate variability were monitored before cycling and 1-4h after the start of cycling. Bayesian hierarchical models were used to examine the relationship between 26 VOCs and acute changes in clinical outcomes adjusted for potential confounding factors.

Results: Each inter-quartile range (IQR) increase in propane/butane exposure was associated with a 2.0 millisecond (ms) (95% CI: 0.65, 3.2) increase in SDNN (standard deviation of normal-to-normal intervals), a 24 ms(2) (95% CI: 6.6, 41) increase in HF (high frequency power), and a 65 ms(2) (95% CI: 11, 118) increase in LF (low frequency power) in the hours following cycling. IQR increases in ethane and isoprene were associated with a 5.8 ms (95% CI: -9.8, -1.7): decrease in SDNN and a 24 ms(2) (95% CI: -44, -7.9) decrease in HF, respectively. IQR increases in benzene exposure were associated with a 1.7 ppb (95% CI: 1.1, 2.3) increase in exhaled nitric oxide and each IQR increase in 3-methylhexane exposure was associated with a 102 mL (95% CI: -157, -47) decrease in forced expiratory volume in 1-s.

Conclusions: Exposure to traffic-related VOCs may contribute to acute changes in lung function, inflammation, or heart rate variability.
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http://dx.doi.org/10.1016/j.envres.2012.06.005DOI Listing
October 2012

Prevalence of autoimmune inflammatory myopathy in the first nations population of Alberta, Canada.

Arthritis Care Res (Hoboken) 2012 Nov;64(11):1715-9

University of Calgary, Alberta, Canada.

Objective: To estimate the population-based prevalence of autoimmune inflammatory myopathy (AIM) in Alberta, Canada, with a specific focus on rates in the First Nations population.

Methods: Physician billing claims and hospitalization data for the province of Alberta (1994-2007) were used to estimate the probability of having AIM (i.e., polymyositis or dermatomyositis) based on 3 case definitions. A latent class Bayesian hierarchical regression model was employed to account for the imperfect sensitivity and specificity of billing and hospitalization data in case ascertainment. We accounted for demographic factors of sex, age group, and location of residence (urban or rural) in estimating the prevalence rates within the First Nations and non-First Nations populations.

Results: The overall prevalence of AIM was 25.0 per 100,000 persons (95% credible interval [95% CrI] 13.4-49.0) in the First Nations population and 33.8 (95% CrI 28.9-39.6) in the non-First Nations population. For both groups, prevalence was increased in women relative to men, rural women relative to urban women, and in those age >45 years.

Conclusion: Unlike other rheumatic diseases such as rheumatoid arthritis, systemic lupus erythematosus, and systemic sclerosis, we did not detect an increased prevalence of AIM in Alberta's First Nations population relative to the non-First Nations population. Potential limitations include coding errors, underidentification of First Nations members, and recognized differences in access to care for the First Nations population.
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http://dx.doi.org/10.1002/acr.21743DOI Listing
November 2012

Comparison of transradial and femoral approaches for percutaneous coronary interventions: a systematic review and hierarchical Bayesian meta-analysis.

Am Heart J 2012 Apr;163(4):632-48

Quebec Heart and Lung Institute, Quebec City, Quebec, Canada.

Background: Despite lower risks of access site-related complications with transradial approach (TRA), its clinical benefit for percutaneous coronary intervention (PCI) is uncertain. We conducted a systematic review and meta-analysis of clinical studies comparing TRA and transfemoral approach (TFA) for PCI.

Methods: Randomized trials and observational studies (1993-2011) comparing TRA with TFA for PCI with reports of ischemic and bleeding outcomes were included. Crude and adjusted (for age and sex) odds ratios (OR) were estimated by a hierarchical Bayesian random-effects model with prespecified stratification for observational and randomized designs. The primary outcomes were rates of death, combined incidence of death or myocardial infarction, bleeding, and transfusions, early (≤ 30 days) and late after PCI.

Results: We collected data from 76 studies (15 randomized, 61 observational) involving a total of 761,919 patients. Compared with TFA, TRA was associated with a 78% reduction in bleeding (OR 0.22, 95% credible interval [CrI] 0.16-0.29) and 80% in transfusions (OR 0.20, 95% CrI 0.11-0.32). These findings were consistent in both randomized and observational studies. Early after PCI, there was a 44% reduction of mortality with TRA (OR 0.56, 95% CrI 0.45-0.67), although the effect was mainly due to observational studies (OR 0.52, 95% CrI 0.40-0.63, adjusted OR 0.49 [95% CrI 0.37-0.60]), with an OR of 0.80 (95% CrI 0.49-1.23) in randomized trials.

Conclusion: Our results combining observational and randomized studies show that PCI performed by TRA is associated with substantially less risks of bleeding and transfusions compared with TFA. Benefit on the incidence of death or combined death or myocardial infarction is found in observational studies but remains inconclusive in randomized trials.
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http://dx.doi.org/10.1016/j.ahj.2012.01.015DOI Listing
April 2012

Prevalence of systemic lupus erythematosus and systemic sclerosis in the First Nations population of Alberta, Canada.

Arthritis Care Res (Hoboken) 2012 Jan;64(1):138-43

University of Calgary, Calgary, Alberta, Canada.

Objective: To estimate the population-based prevalence of systemic lupus erythematosus (SLE) and systemic sclerosis (SSc) in Alberta, Canada, stratified by First Nations status.

Methods: Physician billing claims and hospitalization data for the province of Alberta (1994-2007) were used to ascertain cases of SLE and SSc using 3 case definitions. A latent class Bayesian hierarchical regression model was employed to account for the imperfect sensitivity and specificity of billing and hospitalization data in case ascertainment. We accounted for demographic factors, estimating prevalence rates for the First Nations and non-First Nations populations by sex, age group, and location of residence (urban/rural).

Results: Our model estimated the prevalence of SLE in Alberta to be 27.3 cases per 10,000 females (95% credible interval [95% CrI] 25.9-28.8) and 3.2 cases per 10,000 males (95% CrI 2.6-3.8). The overall prevalence of SSc in Alberta was 5.8 cases per 10,000 females (95% CrI 5.1-6.5) and 1.0 case per 10,000 males (95% CrI 0.7-1.4). First Nations females over 45 years of age had twice the prevalence of either SLE or SSc relative to non-First Nations females. There was also a trend toward higher overall SLE prevalence in urban dwellers, and higher overall SSc prevalence in rural residents.

Conclusion: First Nations females older than 45 years of age have an increased prevalence of either SLE or SSc. This may reflect a true predominance of autoimmune rheumatic diseases in this demographic, or may indicate systematic differences in health care delivery.
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http://dx.doi.org/10.1002/acr.20656DOI Listing
January 2012

Modeling continuous diagnostic test data using approximate Dirichlet process distributions.

Stat Med 2011 Sep 22;30(21):2648-62. Epub 2011 Jul 22.

Department of Epidemiology and Biostatistics, McGill University, 1020 Pine Avenue West, Montreal, Quebec, H3A 1A2, Canada.

There is now a large literature on the analysis of diagnostic test data. In the absence of a gold standard test, latent class analysis is most often used to estimate the prevalence of the condition of interest and the properties of the diagnostic tests. When test results are measured on a continuous scale, both parametric and nonparametric models have been proposed. Parametric methods such as the commonly used bi-normal model may not fit the data well; nonparametric methods developed to date have been relatively complex to apply in practice, and their properties have not been carefully evaluated in the diagnostic testing context. In this paper, we propose a simple yet flexible Bayesian nonparametric model which approximates a Dirichlet process for continuous data. We compare results from the nonparametric model with those from the bi-normal model via simulations, investigating both how much is lost in using a nonparametric model when the bi-normal model is correct and how much can be gained in using a nonparametric model when normality does not hold. We also carefully investigate the trade-offs that occur between flexibility and identifiability of the model as different Dirichlet process prior distributions are used. Motivated by an application to tuberculosis clustering, we extend our nonparametric model to accommodate two additional dichotomous tests and proceed to analyze these data using both the continuous test alone as well as all three tests together.
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http://dx.doi.org/10.1002/sim.4320DOI Listing
September 2011

Prolonged corrected QT interval in anti-Ro/SSA-positive adults with systemic lupus erythematosus.

Arthritis Care Res (Hoboken) 2011 Jul;63(7):1031-7

McGill University, Montreal, Quebec, Canada.

Objective: To examine whether anti-Ro/SSA antibodies are associated with an increased risk of corrected QT (QTc) prolongation, and to study the stability of this relationship over time.

Methods: Patients fulfilling the American College of Rheumatology (ACR) criteria for systemic lupus erythematosus (SLE) were invited to undergo a 12-lead resting electrocardiogram (EKG) in the pilot phase of our project, performed between February 2002 and March 2005. The same study population was used to perform a second similar analysis with a larger sample between April 2005 and May 2007. Multivariate logistic regression models were fit to estimate the cross-sectional association between anti-Ro/SSA and other demographic and clinical variables on QTc prolongation. The other potentially associated factors examined included age, sex, disease duration, lupus activity (Systemic Lupus Erythematosus Disease Activity Index 2000 update), damage (Systemic Lupus International Collaborating Clinics/ACR Damage Index), potassium and magnesium levels, and medications with the potential to prolong the QTc interval.

Results: Cross-sectional analysis of the pilot data (n = 150 patients) showed an association of prolonged QTc with the presence of anti-Ro/SSA (adjusted odds ratio [OR] 12.6; 95% confidence interval [95% CI] 2.3, 70.7). In the second larger study (n = 278), the association was replicated, with a narrower 95% CI (adjusted OR 5.1; 95% CI 1.5, 17.4). In the 118 patients with 2 EKG assessments, the results were consistent over time.

Conclusion: Anti-Ro/SSA was associated with QTc prolongation in both our pilot data and a larger SLE cohort sample. Patients positive for anti-Ro/SSA may benefit from EKG testing and appropriate counseling should be considered for those identified with QTc prolongation.
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http://dx.doi.org/10.1002/acr.20470DOI Listing
July 2011

Drug-eluting or bare metal stents for the treatment of saphenous vein graft disease: a Bayesian meta-analysis.

Circ Cardiovasc Interv 2010 Dec 23;3(6):565-76. Epub 2010 Nov 23.

Institut Universitaire de Cardiologie et de Pneumologie de Québec (Quebec Heart and Lung Institute), Quebec City, Canada.

Background: Observational studies and randomized, controlled trials have yielded uncertain results regarding the benefits of drug-eluting stents (DES) for the treatment of saphenous vein graft (SVG) disease. The objective of this meta-analysis was to assess the cumulative evidence regarding the efficacy and effectiveness of DES to treat SVG compared with bare metal stent (BMS).

Methods And Results: We conducted a bayesian hierarchical meta-analysis of all randomized, controlled trials and observational studies that compared clinical outcomes after DES or BMS placement in SVG disease. Our search resulted in 25 studies, cumulating 5755 patients. DES implantation was not associated with an increased risk of death (odds ratio [OR], 0.85; 95% credible intervals (CrI) [CrI], 0.62 to 1.21) or myocardial infarction (OR, 0.83; 95% CrI, 0.56 to 1.32), but wide CrIs preclude definitive conclusions. Target vessel revascularization (OR, 0.55; 95% CrI, 0.39 to 0.76) and target lesion revascularization (OR, 0.58; 95% CrI, 0.37 to 0.87) were both reduced by approximately 45% with DES. When combining these outcomes, the OR for major adverse cardiac events was reduced in patients treated with DES (OR, 0.62; 95% CrI, 0.46 to 0.81). Finally, the relative risk of stent thrombosis appeared lower with DES, although again the CrIs were very wide (OR, 0.54; 95% CrI, 0.13 to 1.39).

Conclusions: In this study-level meta-analysis, the largest ever reported and the first using bayesian methods, the use of DES for the treatment of SVG disease reduces target vessel revascularization and target lesion revascularization procedures compared with BMS. Although there is no evidence to date to suggest increased rates of mortality, myocardial infarction, or stent thrombosis, further data are needed to address this safety issue.
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http://dx.doi.org/10.1161/CIRCINTERVENTIONS.110.949735DOI Listing
December 2010

Bayesian sample size for diagnostic test studies in the absence of a gold standard: Comparing identifiable with non-identifiable models.

Stat Med 2010 Nov;29(26):2688-97

Department of Epidemiology and Biostatistics, 1020 Pine Avenue West, McGill University, Montreal, Que., Canada H3A 1A2.

Diagnostic tests rarely provide perfect results. The misclassification induced by imperfect sensitivities and specificities of diagnostic tests must be accounted for when planning prevalence studies or investigations into properties of new tests. The previous work has shown that applying a single imperfect test to estimate prevalence can often result in very large sample size requirements, and that sometimes even an infinite sample size is insufficient for precise estimation because the problem is non-identifiable. Adding a second test can sometimes reduce the sample size substantially, but infinite sample sizes can still occur as the problem remains non-identifiable. We investigate the further improvement possible when three diagnostic tests are to be applied. We first develop methods required for studies when three conditionally independent tests are available, using different Bayesian criteria. We then apply these criteria to prototypic scenarios, showing that large sample size reductions can occur compared to when only one or two tests are used. As the problem is now identifiable, infinite sample sizes cannot occur except in pathological situations. Finally, we relax the conditional independence assumption, demonstrating in this once again non-identifiable situation that sample sizes may substantially grow and possibly be infinite. We apply our methods to the planning of two infectious disease studies, the first designed to estimate the prevalence of Strongyloides infection, and the second relating to estimating the sensitivity of a new test for tuberculosis transmission. The much smaller sample sizes that are typically required when three as compared to one or two tests are used should encourage researchers to plan their studies using more than two diagnostic tests whenever possible. User-friendly software is available for both design and analysis stages greatly facilitating the use of these methods.
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http://dx.doi.org/10.1002/sim.4037DOI Listing
November 2010

Adjunctive thrombectomy for acute myocardial infarction: A bayesian meta-analysis.

Circ Cardiovasc Interv 2010 Feb 26;3(1):6-16. Epub 2010 Jan 26.

Department of Medicine, Echocardiography, and Noninvasive Cardiology Service, Montreal Heart Institute, Canada.

Background: In available trials and meta-analyses, adjunctive thrombectomy in acute myocardial infarction (MI) improves markers of myocardial reperfusion but has limited effects on clinical outcomes. Thrombectomy devices simply aspirate thrombus or mechanically fragment it before aspiration. Simple aspiration thrombectomy may offer a distinct advantage.

Methods And Results: We identified 21 eligible trials (16 that used a simple aspiration thrombectomy device) involving 4299 patients with ST-segment elevation MI randomized to reperfusion therapy by primary percutaneous coronary intervention with or without thrombectomy. By using Bayesian meta-analysis methods, we found that thrombectomy yielded substantially less no-reflow (odds ratio [OR], 0.39; 95% credible interval [CrI], 0.18 to 0.69), more ST-segment resolution > or =50% (OR, 2.22; 95% CrI, 1.60 to 3.23), and more thrombolysis in myocardial infarction/myocardial perfusion grade 3 (OR, 2.50; 95% CrI, 1.48 to 4.41). There was no evidence for a decrease in death (OR, 0.94; 95% CrI, 0.47 to 1.80), death, recurrent MI, or stroke (OR, 1.07; 95% CrI, 0.63 to 1.92) with thrombectomy. Restriction of the analysis to trials that used simple aspiration thrombectomy devices did not yield substantially different results, except for a positive effect on postprocedure thrombolysis in myocardial infarction grade 3 flow (OR, 1.49; 95% CrI, 1.14 to 1.99).

Conclusions: In this Bayesian meta-analysis, adjunctive thrombectomy improves early markers of reperfusion but does not substantially effect 30-day post-MI mortality, reinfarction, and stroke. The use of aspiration thrombectomy devices is not associated with a reduction in post-MI clinical outcomes. Thrombectomy is one of the rare effective preventive measures against no-reflow.
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http://dx.doi.org/10.1161/CIRCINTERVENTIONS.109.904037DOI Listing
February 2010

Bayesian estimation of the probability of asbestos exposure from lung fiber counts.

Biometrics 2010 Jun 8;66(2):603-12. Epub 2009 Jun 8.

Department of Epidemiology, Biostatistics and Occupational Health, McGill University, 1020 Pine Avenue West, Montreal, Quebec, H3A 1A2, Canada.

Asbestos exposure is a well-known risk factor for various lung diseases, and when they occur, workmen's compensation boards need to make decisions concerning the probability the cause is work related. In the absence of a definitive work history, measures of short and long asbestos fibers as well as counts of asbestos bodies in the lung can be used as diagnostic tests for asbestos exposure. Typically, data from one or more lung samples are available to estimate the probability of asbestos exposure, often by comparing the values with those from a reference nonexposed population. As there is no gold standard measure, we explore a variety of latent class models that take into account the mixed discrete/continuous nature of the data, that each subject may provide data from more than one lung sample, and that the within-subject results across different samples may be correlated. Our methods can be useful to compensation boards in providing individual level probabilities of exposure based on available data, to researchers who are studying the test properties for the various measures used in this area, and more generally, to other test situations with similar data structure.
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http://dx.doi.org/10.1111/j.1541-0420.2009.01279.xDOI Listing
June 2010

Antiphospholipid antibodies predict imminent vascular events independently from other risk factors in a prospective cohort.

Thromb Haemost 2009 Jan;101(1):100-7

Division of clinical Epidemiology, Department of Medicine, McGill University Health Centre, Montreal, Quebec, Canada.

Antiphospholipid antibodies (aPL) are associated with vascular events, but the magnitude of this risk, alone, or in combination with other atherogenic and thrombophilic risk factors, remains unclear. A prospective cohort of 415 persons was studied for arterial and venous events (AE and VE) over a median time of 7.4 years. aPL and coagulation abnormalities were measured upon beginning of the study and annually for the first four years. Within the cohort, a nested case-control study was conducted to investigate the role of endothelial and inflammatory markers in predicting new vascular events. Forty-five individuals had new vascular events: 18 occurred during the first year of follow-up. The proportion of event-free survivors at eight years was 90% (95%CI = 87%, 94%) for aPL-negative and 72% (60%, 85%) for aPL-positive individuals, respectively. Predictors for new AE were previous AE (HR = 5.7 [2.7, 12.0]), diabetes (5.6 [2.4, 13.2]), aPL positivity (2.6 ([1.2, 5.9]), and age (1.04 [1.01, 1.07]). New VE were predicted by previous VE (6.1 [1.9, 19.9]), anti-beta2-glycoprotein I (abeta2GPI) positivity (5.8 [1.4, 24.1]), activated protein C resistance (APCR) (4.1 [1.1, 15.1]), and gender (3.7 [1.1, 12.9]). In the nested case-control study, similar predictors were observed for AE, while abnormal APCR (OR = 5.5 [1.1, 26.6]) and elevated von Willebrand factor (vWF) (OR = 5.0 [1.2, 19.8]) best predicted VE. We demonstrate that aPL independently predict new vascular events and discriminate between individuals with and without events in the first two years of follow-up, indicating that aPL are associated with a short-term risk of developing new and recurrent vascular events.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3435426PMC
January 2009
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